title: In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony.
abstract: Mycoplasma mycoides mycoides Small Colony (MmmSC) is the causative agent of contagious bovine pleuropneumonia (CBPP), which is responsible for major economic losses in sub-Saharan Africa. Current control relies on live attenuated vaccines, which are of limited efficacy, and antimicrobials are now being assessed as an alternative or adjunct to vaccination. The objective of this study was to determine the in vitro effector kinetics of the macrolide antimicrobial, gamithromycin, against MmmSC in artificial medium and adult bovine serum. Furthermore, it was determined if any differences in gamithromycin activity between these two matrices were mirrored by the older macrolides, tylosin and tilmicosin. Minimum inhibitory concentrations (MICs) for gamithromycin, tylosin and tilmicosin against MmmSC strains B237 and Tan8 were determined in artificial medium and serum. Time-kill curves were constructed at concentrations corresponding to multiples of the MIC for all three macrolides in artificial medium and for gamithromycin in serum. Data were fitted to sigmoid Emax models. Post-antibiotic effects (PAE) were established by exposing strain B237 to antimicrobials at 10× MIC for 1h and monitoring mycoplasma growth thereafter. MICs for gamithromycin, tylosin and tilmicosin were 64-, 8- and 64-fold lower, respectively, in serum than in artificial medium at an inoculum size of 10(6)cfu/mL B237. A similar pattern emerged for Tan8. All three antimicrobials were mycoplasmastatic with maximum effects of -0.44, -0.32 and -0.49log10(cfu/mL) units for gamithromycin, tylosin and tilmicosin, respectively, against B237 in artificial medium. Tylosin and tilmicosin elicited longer PAEs than gamithromycin. In conclusion, gamithromycin, tylosin and tilmicosin all demonstrated in vitro efficacy against MmmSC and represent potential candidates for clinical studies to assess their therapeutic effect against CBPP.
authors.affiliation: Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, United Kingdom. Electronic address: jdmitchell@rvc.ac.uk.
authors.forename: John D
authors.initials: JD
authors.lastname: Mitchell
authors.forename: Shan
authors.initials: S
authors.lastname: Goh
authors.forename: Quintin A
authors.initials: QA
authors.lastname: McKellar
authors.forename: Declan J
authors.initials: DJ
authors.lastname: McKeever
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D018942:Macrolides / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009176:Mycoplasma mycoides / Q000145:classification* / Q000187:drug effects*; D015645:Tylosin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D018942:Macrolides; C052319:tilmicosin; D015645:Tylosin; C552399:gamithromycin
keywords: Contagious bovine pleuropneumonia; Gamithromycin; Mycoplasma mycoides subspecies mycoides Small Colony; Tilmicosin; Tylosin